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95 Cards in this Set
- Front
- Back
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what is haptoglobin. when do its levels change?
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an alpha2-globulin that binds free hemoglobin. when hemolysis occurs it binds hemoglobin so that it isnt released into the urine. eventually the complexes are broken down into bilirubin. so in hemolysis its serum values decrease.
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caues of intravascular hemolysis
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mechanical injury
complement fixation intracellular parasites exogenous toxic factors |
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if free hemoglobin isnt bound to haptoglobin, what happens?
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oxidizes to methemoglobin, which is brown in color. kidney tries to break it down but some gets out into urine
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differences in symptoms between intra and extra hemolysis
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both - anemia, jaundice
E - splenomegaly I - hemoglobinemia, hemoglobinuria, hemosiderinuria |
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bone marrow changes in hemo anemia
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increased numbers of erythroid precursors (normoblasts) in the marrow.
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structure of RBC cell membrance
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alpha and beta spectrin.
spectrin binds ankyrin/band 4.2 which binds the spectrin to transmembrane ion transporter band 3 protein 4.1 binds the tail of spectrin to transmembrane protein, glycophorin A |
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problems with RBC cell membrane proteins cause?
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hereditary spherocytosis
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RBC problems in HS cause?
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RBC life down to 10-20 days. cells become hard and spherical and get trapped in spleen
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abnormally small, dark-staining (hyperchromic) red cells lacking the central zone of pallor
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HS
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MCHC in HS
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increased due to loss of K and H2O
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aplastic crisis in HS caused by?
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parvovirus infection. kills RBC progenitors, ceasing RBC production. and b/c of short life of HS rbcs, this can be bad
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problems in G6PD deficiency
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G6PD is needed to reduce NADP to NADPH while oxidizing G6P in the process. NADPH is needed to convert oxidized glutathione to reduced gluathione, which protects against oxidant injury
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episodic hemolysis in G6PD defi caused by?
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incidents that increase oxidative stress; infection, drugs, certain foods (fava beans)
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histo for G6PD defi
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high levels of oxidants cause cross linking of sulfhydryl groups on globin chains, which becomes denatured and makes membrane boudn precipitates known as heinz bodies. these can either cause intra hemo or can be bitten out my macros in the spleen.
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SC replacement?
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glutamate with valine
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when do SCs sickle?
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when oxygen is released
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MCHC affect on SC
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increased makes it worse
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areas prone to sickling?
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microvascular beds with slow flow. spleen, bone marrow, and inflamed tissue
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SC affect on spleen
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chronic erythrostasis leads to splenic infarction, fibrosis, and shrinkage - autosplenectomy
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SC affect on kidney
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damage to renal medulla that causes hyposthenuria ( inability to concentrate)
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treat for SC
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hydroxyurea - inhibitor of DNA synthesis
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chromosomes needed for HbA
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16 - alpha
11 - beta |
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most common cause of beta+ thalassemia
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splicing mutation
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most common cause of B-0 thalassemia
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chain terminator mutation
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RBCs in thalassemia
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microcytic, hypochromic
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RBC damage in beta thalassemia
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decreased B causes increased alpha which precipitate forming insoluble inclusions, prone to extra hemo
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beta thalassemia complications?
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innefective erythropoiesis combined with anemia leads to massive erythroid hyperplasia in marrow and extensive extramedullary hematopoiesis
ineffective erythropoiesis suppresses hepcidin, causing increased blood iron levels |
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retic count in beta thalassemia
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elevated but lower than expected due to bad erythropoiesis
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normoblasts (poorly hemoglobinized nucleated red cell precursors) seen in?
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thalassemia
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- alpha, alpha alpha
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silent carrier
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- - , alpha alpha
- alpha, - alpha |
alpha thalassemia trait (asympt)
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- - , - alpha
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HbH disease. tetramers of B-globin form - has extremely high affinity for oxygen
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- - , - -
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hydrops fetalis. excess gamma-globin chains form tetramers (barts) that have extremely high affinity for O2. survival early on due to zeta chains.
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PNH (paroxysmal nocturnal hemoglobinuria) mutation
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phosphatidylinositol glycan complemntation group A gene (PIGA) - an enzyme essential for the synthesis of ceterin cell surface proteins
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PNH causes hemolysis how?
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PNH cells deificent in proteins that regulate complement activity. So they get attacked by membrane attack complex, causing intravascular hemolysis
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PNH at night why?
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decrease in pH activated complement
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complications with PNH
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thrombosis due to platelets problems. and low NO by free hemoglobin
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lack of CD55 and CD59
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PNH
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test of immunohemolytic anemia
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direct coombs anitglobulin tests
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immunohemolytic anemia: 3 types
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warm antibody - IgG above 37
cold aggluti - IgM below 37 cold hemolysin - IgG below 37 |
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warm antiobody hemolysis how
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IgG binds to RBC and gets eaten by macro in spleen, similar to SH
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drugs that cause warm antibody
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penicillin, cehpalosporins, alpha-methlydopa
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immunohemolytic anemia antibodies directed against?
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Rh blood groups in warm antibody
? for cold agglutin P group of RBC in cold hemolysin |
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virus associated immunohemolyic anemia
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cold agglutinin. raynauds. (not too bad because IgM gets released when it gets back to center of body)
or cold hemolysin in kids following viral infection |
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cold hemolysin anitbodies bind what?
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P blood group aniten on RBC surface in cool periphery. when IgG binds it comes back to center and complement is more activated at higher temps
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when are schistocytes seen?
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hemolytic anemia resukting from trauma to red cells - burr, helmet, triangle cells
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B12 and folic acid needed for syn of?
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thymidine, one of the dour bases found in DNA
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presence of red cels that are macrocytic and oval
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megaloblastic anemias
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neutrophils are larger than normal and hypersegmented, having five or more nuclear lobules instead of normal 3-4
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megaloblastic anemias
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bone marrow state in megaloblastic anemias
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hypercellular.
megaloblastic changes detected at all stages of erythroid development granulocytic precursors display dysmaturation in the form of giant metamyelocytes and band forms |
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b12 path to ileum
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bound to proteins initially. in stomach pepsin releases it from proteins, and R group from the saliva binds to it
in duo b12 is released from R by pancreatic proteases and associates with IF bind to IF receptor in ileum and associates with transcobalamin II which delivers it to liver and other cells of the body |
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cobalamin = ?
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b12
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b12 needed for what 2 reactions
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reaction that creates methionine and FH4 from homocystein and N5-methyl FH4 (all via methionine synthase)
neuro - conversion of methlymalonyl CoA to succinyl CoA. leading to increaed formation and incorporation of fatty acids into neuronal lipids, causing demylenation. (not fixed by FH4 administration) |
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FH4 needed for?
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conversion of dUMP to dTMP
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pernicious anemia?
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b12 defi
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NALP1
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pernicious anemia
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spinal cord affects in pernicous anemia
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demylenation of dorsal and lateral tracts
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elevated levels of what in PA
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methylmalonic acid
homocysteine - atherosclerosis and thrombosis |
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FH4 admin can make what worse?
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neuro component of b12 defi
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what is required for hemoglobin synthesis?
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iron
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ferritin found where?
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parenchymal cells in liver. macros in spleen and BM
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hepatocyte and macros get their iron how?
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H - from transferrin
M - RBC breakdown |
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how is iron absorbed?
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Fe3 to Fe2 by dudodenal cytochrome B. Fe2 through DMT 1 on luminal side and ferroportin 1 on basolateral side (can be blocked by hepcidin). Fe2 to Fe3 by hephaestin or ceruloplasmin. Fe3 binds to transferrin
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hepcidin does what?
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blocks absorption an duo and release from macrophages which are important source of iron that is used by erythroid precursors to make hemoglobin
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if iron levels are high, what happens at duo?
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iron turned in mucosal ferritin in duo cells and shed
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TMPRSS6 mutation
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hepatic transmembrane serine protease that normally suppresses hepcidin production when irons stores are low. pts have high hepcidin and low iron and fail to respond to iron therapy
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iron defi anemia type?
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microcytic hypochromic
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pencil cells and enlarged central area of pallor
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iron defi anemia
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pathogenesis of anemia of chronic disease
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chronic inflammation causes release of IL-6 that increase hepcidin. blocks release of iron from macros, which is needed by developing erythroid precursors.
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labs in anemia of chronic disease
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low iron and low total iron bidngin capacity, lots of iron in macros. elevated ferritin
low erythroptein, cause by hepcidin |
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anemia of chronic disease protects from?
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H influenzae
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histo for aplastic anemia
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hypocellular bone marrow - as apposed to hypercellular in myeloid neoplasms
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no splenomegaly
pancytopenia low retic count |
aplastic anemia
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pathogenesis for aplastic anemia
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environmental insult or auto immune does damage to stem cells which express new antigens and activate t cell response
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aplastic crisis?
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persons with moderate to severe hemolytic anemia gets infected with parvovirus B19.
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form of marrow failure in which space occupying lesions replace normal marrow
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myelophthisic anemia (tear drop cells)
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inherited defects that lead ot stabilization of HIF-1alpha
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hypoxia induced factor that stimulates the transcription of erythropoietin gene
(PCV) |
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autosomal dominant disorder characterized by dilated, tortuous blood vessels with thin walls that bleed readily
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hereditary hemorrhagic telangiectasia
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hypersensitivity disease that results from deposition of circulation immune complexes within vessels
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henoch-schonlein purpura
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women, under 40, pinpoint hemorrhages, ecchymoses, low platelet, normal or increasd megak in bm, large platelets in peripheral blood, normal pt ptt
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chronic immune thrombocytopenic purpura
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drugs most common for thrombocytopenia
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quinine, quinidine, vancomycin, heparin
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occurs 5-14 days after heparin administration rarely
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type 2 thrombocytopenia - antibodies recognize complexes of heparin and platelet factor 4, promotes thrombosis
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deficiency in ADAMTS13? function?
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TTP
degrades vWF. in absense they accumulate and promote activation and agg |
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type 1 HUS
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E. coli - shiga toxin causes platelet agg
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problem in hus 2
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lack proteins that normally act to prevent activation of alternative complement pathway
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defi in complex Ib-IX
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bernard soulier
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defi in IIb-IIIa
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glanzmann thrombasthenia
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types of vWF disease
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1 - mild vWF defi
3 - severe vWF defi 2 - norma amount of vWF but it is defective |
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how to treat vWF disease
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desmopressin stimulates vwf realase
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hemo A - high levels of thrombin needed to activate what?
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TAFI (thrombin activated fibrinolysis inhibitor) - not enough thrombin so this isnt activated
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two major mechanisms for DIC
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1 - release of tissue factor or thromboplastic substances into circ
2 - wide spread injury to endothelial cells |
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important mediator in DIC
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TNF - induces endothelial cells to express tissue factor on their cell surfaces and to decrease the expression of thrombomodulin, shifting the checks and balances that govern hemostasis towards coagulation
also up regulates expression of adhesion molecules |
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howell jolly bodies?
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DNA remnants. During maturation in the bone marrow erythrocytes normally expel their nuclei, but in some cases a small portion of DNA remains.
sickle cell |
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hypersegmented granulocytes
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pernicious anemia
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transient neurological probles
fever thrombocytopenia microangiopathic hemolytic anemia acute renal failure |
TTP
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